Evaluation of Potential Antigen-specific Host Biomarkers in QuantiFERON Supernatants as Candidates for the Diagnosis of Ocular Tuberculosis.

Purpose: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB).Methods: We investigated 47 host markers in QuantiFERON supernatants from 92 individuals with uveitis using the Luminex platform. We evaluated the potential of individual and combined biomarkers to distinguish between patients with possible, probable, and no OTB.Results: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1ß, in individuals with OTB versus no OTB regardless of HIV status. Individuals with probable and possible OTB only differed regarding GM-CSF. We identified a four-marker biosignature (CD40 L, IL-33, IFN-γ, and SAP) which diagnosed OTB with an area under the ROC curve of 0.80, sensitivity = 56.3% and specificity = 90.0%.Conclusion: This represents the first attempt at screening QuantiFERON supernatants for biomarkers to diagnose OTB. We identified candidate biosignatures which may aid in diagnosing OTB in both HIV positive and negative patients.

Longitudinal analysis of serum cytokine profile among patients with tubercular multifocal serpiginoid choroiditis: a pilot study.

PURPOSE: To analyze the serum cytokines profile in patients with tubercular multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy (ATT) and oral corticosteroids. METHODS: In this prospective longitudinal study, patients with active TB MSC were included. Serum levels of interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α were analyzed using bead-based immunoassay. The levels of transforming growth factor (TGF)-ß were measured using cytokine bead array. Serial measurement was performed at baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing paradoxical worsening (PW) of TB MSC were identified and their serum levels of cytokines were compared with those patients who showed healing of lesions. Comparison of cytokine levels with baseline values was also performed. RESULTS: Twelve patients (three females) were included in the study. Four patients showed paradoxical worsening of TB MSC at 3.2 ± 1 weeks after initiation of therapy. Compared to patients who showed healing of lesions, patients with PW showed higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW, levels of IFN-γ peaked at 1 week ((p = 0.01) and levels of TNF-α peaked at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed healing. There was no significant difference in TGF-ß levels at any time point in either group (p > 0.47). CONCLUSIONS: Baseline and serial levels of inflammatory serum cytokines may help in predicting the response to ATT and corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in pro-inflammatory cytokines after initiation of ATT indicating higher bacillary load.

Utility of QuantiFERON®-TB Gold test in diagnosis and management of suspected tubercular uveitis in India.

The tuberculin skin test, used to detect latent systemic tuberculosis (TB), has its limitations. The utility of interferon-gamma assays, found useful in the diagnosis of latent TB, is still unestablished in tubercular uveitis. We present the results of QuantiFERON(®)-TB Gold (QFT-G) test and its relevance in the diagnosis and management of suspected tubercular uveitis in India. All suspected tubercular uveitis patients seen at our uveitis clinic between October 2006 and June 2008 who underwent relevant blood investigations, chest X-rays, Mantoux tests and QFT-G tests were included. Clinical profile, systemic correlation and outcome with treatment were analysed. Fifty suspected tubercular uveitis patients underwent QFT-G testing. The age range of the patients was 6-55 years (mean 32.66 years). Seven patients presented with active and three with a past history of systemic TB. The QFT-G test was positive in 29 patients. Radiological findings of TB were seen in four patients with a positive QFT-G and one patient with a negative QFT-G test. In 11 patients both QFT-G and Mantoux tests were positive. Eighteen Mantoux-negative patients were QFT-G-positive. Significantly, no patient with a positive Mantoux had a negative QFT-G test. Of the 32 patients with posterior uveitis, 17 patients had serpiginous choroiditis, four patients had a choroidal granuloma, six patients had multifocal choroiditis, four patients had retinal vasculitis, and one patient had a subretinal abscess. All QFT-G-positive patients were treated with anti-tuberculosis therapy as well as systemic steroids with a favorable clinical outcome. Our study shows that the QFT-G test is very useful in the diagnosis and management of suspected ocular TB. It was found to be very sensitive in identifying latent TB patients who, upon treatment, had a significantly reduced frequency of recurrences. It was more sensitive than the Mantoux test and is not significantly affected by previous treatment with systemic steroids or immunosuppressives. A negative QFT-G test can also be used as an adjunct before initiation of systemic steroids or immunosuppressives in uveitic patients particularly in an endemic setting like India.

Utility of QuantiFERON TB gold test in a south Indian patient population of ocular inflammation.

AIM: To study the utility of interferon-g release assays (QuantiFERON TB gold test) in a south Indian patient population of intraocular inflammation. DESIGN: Evaluation of a diagnostic test- a pilot study from January 2007 to October 2008. MATERIALS AND METHODS: QuantiFERON TB gold test was performed on the following groups of patients following an informed consent. Group A included healthy volunteers without any exposure to tuberculosis (TB) or past history of TB (n=22). Group B included patients with active systemic TB diagnosed by the demonstration of acid-fast bacilli or by the histopathology finding of caseation with granuloma formation from the sputum, lymph node, skin or intestinal biopsies (n=26). Group C included patients with uveitis of known etiologies other than intraocular TB without any history of exposure to active TB (n=21). Group D included patients with a diagnosis of presumed intraocular TB, who responded to antitubercular therapy by decreased or no recurrences following treatment and with a minimum of nine months follow-up following initiation of antitubercular therapy (n=39). RESULTS: The sensitivity and specificity of the QuantiFERON TB gold test to pick up active systemic TB was 58% and 77% respectively. The sensitivity and specificity of the QuantiFERON TB gold test to pickup intraocular TB was 82% and 76% respectively. CONCLUSIONS: QuantiFERON TB gold test alone may not be specific for intraocular TB. The significance of this test in a case scenario needs to be interpreted with clinical presentation and other evidences for intraocular TB.